Biomedical subjects

A Afek

Publications and source records attributed to A Afek.

40 records · Page 3Linked to original sources

PubMed1995

Bromocriptine immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells.

Bromocriptine (BRC) is a dopamine agonist that suppresses the secretion of prolactin by the pituitary gland and is known to have immunomodulating properties. In the present study, we investigated the effect of BRC on the development of two autoimmune experimental models: (i) systemic lupus erythematosus (SLE), induced by injection of a human anti-dsDNA monoclonal antibody (MIV-7); (ii) primary anti-phospholipid syndrome (PAPS), induced by injection of a mouse anticardiolipin monoclonal antibody (CAM). BRC had a suppressive effect on in vivo autoantibody production, as well as on the appearance of other manifestations of the respective disease. The BRC activity seems to be nonspecific, since the same effect was demonstrated in mice with lupus and with PAPS. These data were supported by the in vitro nonspecific effect of CD8 cells induced in vivo by bromocriptine, on specific lymph node cell proliferation in the presence of the pathogenic monoclonal antibodies (MIV-7 or CAM, respectively), and on the response to an irrelevant autoantigen, myelin basic protein. These data were complemented by the nonspecific suppressive effect by the T-suppressor factor, produced by the CD8 cells, on specific thymidine uptake by lymph node cells from experimental SLE or PAPS in the presence of the immunizing mAb. Injection of CD8 cells from BRC-treated mice with SLE or PAPS abolished the disease development in the lupus and PAPS experimental models. The data suggest a possible novel role of bromocriptine in downregulating autoimmune phenomena through induction of natural nonspecific CD8+ suppressor cells.

Animals↗

PubMed1995

Abrogation of experimental systemic lupus erythematosus and primary antiphospholipid syndrome with intravenous gamma globulin.

OBJECTIVE: To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')2, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')2 as inhibitor. RESULTS: Following treatment with IVGG or IVGG F(ab')2, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDAN and aCL antibodies in the IVGG preparation. CONCLUSION: Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.

Animals↗

PubMed1995

Induction of Goodpasture antibodies to noncollagenous domain (NC1) of type IV collagen in mice by idiotypic manipulation.

The characteristic pathogenic autoantibodies in Goodpasture's syndrome (GPS) are directed to the noncollagenous domain (NC1) of basement membrane type IV collagen. To examine whether immunization with anti-NC1 antibodies could lead to GPS-like pathology, naive BALB/c mice were immunized intradermally with a mouse IgG anti-NC1 monoclonal antibody or IgG serum fraction derived from patients with GPS. Mice immunized with normal mouse or human IgG and nonimmunized mice served as controls. Anti-NC1 antibodies of IgG isotype were detected in the sera of mice injected with anti-NC1 antibodies, but not in the sera of control mice. The presence of circulating anti-NC1 antibodies coincided in some of the mice erythrocyturia or proteinuria and pathological changes in the kidneys. No pathologic alterations were seen in the control mice. The results show that specific idiotypic manipulation can induce anti-NC1 antibodies and pathological changes resembling human GPS.

Animals↗

PubMedDate not supplied

Valvular deposition of antiphospholipid antibodies in the antiphospholipid syndrome: a clue to the origin of the disease.

In this report we present an unusual case of a 45-year-old female patient with systemic lupus erythematosus (SLE) who was hospitalized for mitral valve replacement. In her childhood she presented with mitral stenosis and chorea on which grounds a preliminary diagnosis of rheumatic fever was established. After a quiescent period lasting two decades her disease erupted with mitral stenosis, thromboembolic phenomena, and nephritis. Due to severe malfunctioning of her mitral valve, the patient eventually underwent mitral valve replacement. The antibodies involved in the pathogenesis of our patient's valvular disease were studied by immunohistochemical analysis, applying rabbit polyclonal anti-human IgG and IgM anti-human C3c and anti-idiotypes to a mouse monoclonal naturally occurring polyspecific human monoclonal anti-cardiolipin antibody termed S2.9, and to the 16/6 Id which defines a common Id on anti-DNA antibodies in patients with SLE. Immunoperoxidase staining using an anti-idiotype mAb to anti-cardiolipin antibodies demonstrated the deposition of these anti-bodies in the subendothelial layer of the valve. We believe that anti-phospholipid syndrome (APS) with SLE was the initial and primary disease in this patient. These findings clearly indicate that APS must be considered in the differential diagnosis of rheumatic fever, particularly in young female patients who present with mitral stenosis and chorea.

Adolescent↗